Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital, Xi'an Jiaotong University, No.157, Xi Wu Lu, Xi'an 710004, Shaanxi Province, China.
Cell Biol Int. 2018 Sep;42(10):1300-1310. doi: 10.1002/cbin.11002. Epub 2018 Jun 29.
Human cholesteatoma perimatrix fibroblasts (hCPFs) can stimulate the endothelial cells of nearby microvessels to proliferate and migrate in a paracrine manner. Exosomes, secreted from various cell types, are one of the most important paracrine factors and play critical roles in intercellular communication. However, whether exosomes derived from human cholesteatoma perimatrix fibroblasts (hCPFs-Exo) can promote angiogenesis has not been reported. In this study, we isolated exosomes secreted by hCPFs and observed that hCPFs-Exo was able to promote migration and tube formation in human umbilical vein endothelial cells (HUVECs). Advanced studies revealed hCPFs-Exo with low expression of miR-106b-5p was transferred into HUVECs, and decreased expression of miR-106b-5p could promote angiogenesis by targeting Angiopoietin 2 (Angpt2) via binding to its 3'-UTR. Furthermore, low levels of miR-106b-5p triggered overexpression of Angpt2, and significantly increased HUVEC migration and tube formation. Taken together, our results suggest that hCPFs-Exo transports low expressed exosomal miR-106b-5p to endothelial cells and promotes angiogenesis by overexpression of Angpt2.
人胆脂瘤基质成纤维细胞（hCPFs）可以旁分泌方式刺激附近微血管内皮细胞的增殖和迁移。外泌体是各种细胞类型分泌的最重要的旁分泌因子之一，在细胞间通讯中发挥着关键作用。然而，人胆脂瘤基质成纤维细胞（hCPFs-Exo）衍生的外泌体是否能促进血管生成尚未有报道。在本研究中，我们分离了 hCPFs 分泌的外泌体，并观察到 hCPFs-Exo 能够促进人脐静脉内皮细胞（HUVEC）的迁移和管腔形成。进一步的研究揭示 hCPFs-Exo 中 miR-106b-5p 的表达水平较低，该 miR-106b-5p 被转移到 HUVEC 中后，通过结合其 3'-UTR 靶向血管生成素 2（Angpt2），从而降低 miR-106b-5p 的表达水平能够促进血管生成。此外，miR-106b-5p 的低水平表达会引发 Angpt2 的过表达，显著增加 HUVEC 的迁移和管腔形成。综上所述，我们的研究结果表明 hCPFs-Exo 将低表达的细胞外体 miR-106b-5p 转运至内皮细胞，并通过过表达 Angpt2 促进血管生成。
